Chronic lymphocytic leukemia (CLL) is the most common hematologic disease affecting adults in Western countries. Although CLL remains an incurable disorder, early stage detection and treatment can control disease progression, while late stage patients are often unresponsive to treatments. The abnormal expressions of certain T cell markers by CLL B cells, such as ZAP-70, have been used in the stratification of the disease, i.e., overall survival is significantly worse in ZAP-70 positive cases. Like many other cancers, the diagnosis of the disease is often delayed due to the lack of symptoms in early stages.
Early cancer detection and disease stratification or classification are critical to successful treatment. Accessible, reliable, and informative cancer biomarkers can be medically valuable and could provide some relevant insights for cancer biology. Recent studies have suggested some improvements in detecting malignancies by the use of specific extracellular microRNAs (miRNAs) in plasma. In chronic lymphocytic leukemia (CLL), an incurable hematologic disorder, sensitive, early, and non-invasive diagnosis and better disease classification would be very useful for more effective therapies. These circulating, small non-coding RNA could be sensitive biomarkers for the early stages detection of the disease. We show here that certain miRNAs are present in CLL patient plasma at levels significantly different from healthy controls and from patients affected by other hematologic malignancies. The levels of several of these plasma miRNAs also have shown significant differences between zeta-associated protein 70 (ZAP-70) positive and ZAP-70 negative CLLs. Based on MicroRNA and mRNA expression data, we have identified a putative regulatory network associated with BCL2 and ZAP-70 expression in CLL. This result suggests both the possibility of using the levels of specific miRNAs in plasma to detect early CLL, to determine the ZAP-70 status, and also suggests potential therapeutic approaches that could be combined with already established clinical parameters.